Nomifensine was investigated for use as an antidepressant in the 1970s, and was found to be a useful antidepressant at doses of 50–225 mg per day, both motivating and anxiolytic. There were relatively few adverse effects (mainly dry mouth, headache, nausea), the drug was not sedating, did not interact significantly with alcohol and lacked anticholinergic effects. No withdrawal symptoms were seen after 6 months treatment. The drug was however considered not suitable for agitated patients as it presumably made agitation worse.
Some case reports in the 1980s suggested that there was potential for psychological dependence on nomifensine, typically in patients with a history of stimulant addiction, or when the drug was used in very high doses (400–600 mg per day).
In a 1989 study it has been investigated for use in treating adult ADHD and proven successful. In a 1977 study it has not proven of benefit in advanced parkinsonism, except for depression associated with the parkinsonism.
Due to the risk of a risk of haemolytic anaemia, the U.S. Food and Drug Administration (FDA) withdrew approval for nomifensine on March 20, 1992. Nomifensine has subsequently been withdrawn from the Canadian and UK markets as well. Some deaths were linked to immunohaemolytic anemia caused by this compound although the mechanism remained unclear.
In 2012 structure–affinity relationship data (compare SAR) were published.
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